Novel pyrrolinones



United States Patent 3,272,842 NOVEL PYRRQLINONES Nelson R. Easton and Robert D. Dillard, both of lndianapolis, ind, assignors to Eli Lilly and Company, Indianapolis, End, a corporation of Indiana. No Drawing. Filed June 25, 1965, Ser. No. 467,106 6 Claims. (Cl. 260-3265) This invention relates to certain novel pyrrolinones.

The compounds of this invention are useful in the treatment of crown gall, which is a manifestation in plants of the bacterial disease caused by the organism Agrobacterium tumefaciens. Crown gall is common to many nursery plants, in particular, roses, tomatoes, walnuts, apples, balsam, raspberries, and other plants of commercial importance. At the present time there are no commercial products useful against crown gall except the antibiotic streptomycin. The discovery of any simple, nontoxic, readily available compound useful against this disease, therefore, represents an important advancement in the art. The new compounds are also effective pre emergent and post-emergent herbicides.

The compounds provided by the present invention can be represented by the following formula:

wherein R and R when taken alone, are lower alkyl, phenyl, or substituted phenyl containing no more than two substituents, said substituents being methyl, trifluoromethyl, or halo;

R and R when taken together with the carbon atom to which they are attached, complete a C C cycloalkyl ring;

R is hydrogen, lower alkyl, C -C cycloalkyl, lower alkoxy-lower alkyl, or tetrahydrofurfuryl;

R is hydrogen, lower alkyl, phenyl, or naphthyl;

R is phenyl, monoor di-halo phenyl, phenoxy, monoor di-halo phenoxy, phenylthio, monoor di-halo phenylthio, naphthyl, monoor di-halo naphthyl, naphthyloxy, monoor di-halo naphthyloxy, naphthylthio, monoor dihalo naphthylthio, or thienyl.

Lower alkyl as used herein refers to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec.-butyl, or -tert.- butyl.

Lower alkoxy refers to the lower-alkyl groups above, attached at any available position of the defined loweralkyl group through an intervening oxygen atom. The groups thus include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec.-bu-toxy, or tert.-butoxy.

Halo refers to fiuoro, chloro, bromo, or iodo.

C C cycloalkyl refers to cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

C -C cycloalkyl" refers to cyclopropyl, cyolobutyl, cycloheptyl, or cyclooctyl.

Representative compounds provided by this invention include:

1-methoXyethyl-3 phenoxy-4-benzyl-5,5 diisopropyl- 3-pyrrolin-2-one 1-tert.-butyl-3 (l-naphthyloxy) 4,5,5 triethyl-3- pyrrolin-Z-one 1-cyclobutyl-3 [1-(4-chloronaphthyl)] 4-(2-naphthyl) methyl-5 ,5 -diethyl-3-pyrrolin-2-one 1-ethyl-3-(4-chlorophen0xy) 4-ethyl-5,5 dimethyl-3- pyrrolin-2-one See l-n-butyl 3-(3-fiuorophenyl)-4,5 dimethyl S-isopropyl-3-pyrrolin-2-one 3-(4-fluorophenylthio) S-methyl 4,5-diethyl-3-pyrrolin-Z-one 3-(6-chloro Z-naphthylthio)-4-methyl-5,S-diisopropyl- 3-pyrrolin-2-one 1-isopropoxyethyl-3 (2-bromo-5 fiuorophenyl) 4- methyl-S-ethyl-S-isopropyl-3-pyrrolin-2-one and the like.

The compounds of this invention can be made by the cyclization of the N-acyl derivatives of fi-keto amines, said derivatives being disclosed in our co-pending application Serial No. 461,198, filed June 3, 1965. The cyclization is conveniently carried out in the presence of a strong base such as sodium or potassium hydroxide, or sodium or potassium alkox-ide, typically in a non-aqueous solvent.

Representative examples of the N-acyl derivatives which can be cyclized include:

3-methyl-3-phenoxyacetamido-Z-heptanone 3-isopropyl-4 methyl-3 (p-chlorophenoxyacetamido)- 2-pentanone 3tert. butyl 3 (m-fluorophenoxyacetamido) 2- pentanone 3-ethyl-4,4-dimethyl-3-(2-fluorophenoxyacetamido -2- pentanone 1 phenyl-3 -methyl-3 (3 ,4-diiodophenoxyacetamido -2- pentanone 1-( l-naphthyl -3 -methyl-3 (3 -chloro-4-bromophenoxyacetamido -3-pentanone 2 methyl-2-(3,4-dichlorophenoxyacetamido)-3 hexanone 3,6,8-trimethyl-6-phenoxyacetamido-S-nonanone 1-phenyl-3ethy1-3-(N-cyclohexyl-Z-chlorophenoxyacetamido)-2-pentanone 1 (2-naphthyl)-3-ethyl-3-(N-ethoxyethyl-3-iodophenoxy-acetamido)-2-hexanone 3 isobutyl-3-[N-(-methoxybutyl)-3-bromophenylthioacetami-do]-2-heptanone 3 methyl-3-[N-methyl-2-(4-bromophenoxy) acetamido]-2-butanone 3 methyl-3-[N-methoxyethyl-2-(3-iodophenylthio) acetamidoJ-Z-pentanone N-( l-acetylcyclohexyl) -N-methyl-4-fluorophenoxyacetamide N (l-acetylcyclopentyl)-N-(3 methoxy-2 butyl)-2- (2,6-diiodo-1-naphthyloxy) acetamide N (l-caproylcyclooctyl) N tetrahydrofurfuryl-3,4-

dichloro-2-naphthylthioacetamide Example 1 A mixture of 25 g. of 3-methyl-3-(N-methylphenylacetamido)-2-butanone and 5 g. of potassium hydroxide, finely powdered (98% minimum assay) in 200 m1. of xylene was refluxed for 16 hours. After being cooled, the mixture was filtered and the filtrate distilled in vacuo, yielding 1,4,5,5-tetramethyl-3-phenyl-3-pyrrolin-2-one. Boiling point, 119-124 C. (0.05 mm. Hg). The product spontaneously crystallized and was recrystallized from etherpetroleum ether (boiling range, 30-60 C.). Melting point, 61-63 C.

Analysis.Calcd. for C H NO: C, 78.10; H, 7.96. Found: C, 78.30; H, 7.96.

Example 2 Sixteen grams of sodium metal were dissolved in one liter of absolute ethyl alcohol at elevated temperature. The solution was cooled to room temperature, and 68 g. of 3-methyl-3-phenylacetamido-Z-butanone were added dropwise. The resulting solution was stirred for 3 hours at ambient room temperature. One liter of water and one liter of chloroform were added, and the resulting twolayered mixture was separated. The chloroform layer was dried, the solvents removed, and the residue crystallized from benzene, yielding 35 g. of 4,5,5-trimethyl-3- phenyl-3-pyrrolin-2-one. Melting point, 180 C.

Analysis.-Calcd. for C H NO: C, 77.58; H, 7.51. Found: C, 77.31; H, 7.67.

In addition to the above compound, the following are several other examples of compounds prepared by the same procedure:

1,5,5-trimethyl -3- phenyl -4- ethyl -3- pyrrolin -2- one. Melting point, 1.55160 C.

Analysis.Calcd. for C H NO: C, 78.56; H, 8.35. Found: C, 78.64; H, 8.59.

1 ethyl 3 phenyl-4,5,5-trimethyl-3-pyrrolin-2-one. Boiling point, 123124 C./0.05.

Analysis.-Calcd. for C H NO: C, 78.56; H, 8.35. Found: C, 78.30; H, 8.33.

1,4,5-trimethyl -3- phenyl -5- ethyl -3- pyrrolin -2- one. Melting point, 5860 C.

AnaIysis.Calcd. for C H NO: C, 78.56; H, 8.35. Found: C, 78.46; H, 8.37.

3,5-diphenyl-4,5-dimethyl-3-pyrrolin-2-one. point, 174-176 C.

AnaIysis.-Calcd. for C H NO: C, 82.10; H, 6.51. Found: C, 82.08; H, 6.52.

2-keto-3-phenyl-5-methyl-l-azaspiro [4.5] A -decene. Melting point, 240-242 C.

Analysis-Calcd. for C H NO: C, 79.63; H, 7.93. Found: C, 79.70; H, 7.76.

2 keto-3-(4-chlorophenyl)-4-methyl-l-azaspiro [4.5]- A -decene. Melting point, 251-253 C.

Analysis.-Calcd. for C H ClNO: C, 69.68; H, 6.57. Found: C, 69.47; H, 6.40.

2 keto-3-(3,4-dichlorophenyl)- 4- methyl-1 azaspiro [4.5]-A -decene. Melting point, 227229 C.

Analysis.Calcd. for C H CI NO: C, 61.94; H, 5.52. Found: C, 62.07; H, 5.53.

1,4-dimethyl-2-keto-3 -phenyl- 1 -azapiro 4.5 -A -decene. Melting point, 90-92 C.

Analysis.Calcd. for C H NO: C, 79.96; H, 8.29. Found: C, 80.17; H, 8.32.

Melting 2-keto-3-phenyl-4 methyl-l-azaspiro[4.6]A -undecene.

Melting point, 2l8219 C.

Analysis.Calcd. for C H NO: C, 79.96; H, 8.29. Found: C, 80.15; H, 8.13.

2 keto-3-phenoxy-4-methyl- 1 -azaspiro [4.5 -A -decene. Melting point, 192-194 C.

Analysis.Calcd. for C H NO C, 74.68; H, 7.44. Found: C, 74.34; H, 7.40.

2 keto 3 (3,4-dichlorophenoxy)-4-methyl-l-azaspiro [4.5]-A -decene. Melting point, 214216 C.

Analysis.-Calcd. for C H CI NO C, 58.90; H, 5.25. Found: C, 58.82; H, 5.22.

2 keto 3-(3,4-dichlorophenoxy)-4-methyl-1-azaspiro [4.5]-A -decene. Melting point, 189-191 C.

Alzalysis.Calcd. for C H C1 NO C, 58.90; H, 5.25. Found: C, 58.85;H, 5.38.

2 keto-3-(4-fiuorophenoxy)-4-methy1-1-azaspiro[4.5 A -decene. Melting point, 235237 C.

Analysis.Calcd. for C H FNO C, 69.80; H, 6.58. Found: C, 69.61; H, 6.59.

2 -keto-3-(4-bromophenoxy) -4-methyl-1-azaspiro [4.5 A -decene. Melting point, 207209 C.

Analysis.Calcd. for C H BrNO C, 59.15; H, 5.39. Found: C, 59.28; H, 5.48.

2-keto-3- (4-chlorophenoxy) -1, 4-dimethyl-l-azaspiro [4.5]-A -decene. Melting point, 132-134 C.

Analysis.Calcd. for C H ClNO C, 66.77; H, 6.59. Found: C, 66.98; H, 6.63.

2-keto-3- (3,4-dichlorophenoxy) -1, 4-dimethyl-1-azaspiro-[4.5]-A -decene. Melting point, 118-120 C.

Analysis.Calcd. for C H Cl NO C, 60.01; H, 5.62. Found: C, 60.22; H, 5.77.

4, 5, 5-trimethyl-3- (4-chlorophenylthi0) -3-pyrrolin-2- one. Melting point, 151-153" C.

Arzalysis.-Calcd. for C H CINOS: C, 58.31; H, 5.26. Found: C, 58.08; H, 5.33.

4, 5, 5-trimethyl-3- (4-chlorophenyl) -3-pyrrolin-2-one. Melting point, 188l90 C.

Analysis.Calcd. for C H CINO: C, 66.24; H, 5.98. Found: C, 66.24;H, 6.20.

4, 5, 5-trimethyl-3- (3,4-dichlorophenyl) -3-pyrrolin-2- one. Melting point, 179181 C.

Analysis.Calcd. for C H Cl NO: C, 57.79; H, 4.85. Found: C, 57.80; H, 4.81.

4, 5, 5-trimethyl-3-phenoxy-3-pyrrolin-2-one. point, 132-134 C.

Analysis.-Calcd. for C H NO C, 71.86; H, 6.96. Found: C, 71.58;H, 6.98.

4, 5 ,5 -trimethyl-3- (4-chlorophenoxy) -3-pyrrolin-2-one. Melting point, 146148 C.

Analysis.Calcd. for C H CINO C, 62.03; H, 5.60. Found: C, 62.26; H, 5.80.

4,5,5 trimethyl 3 (3,4 dichlorophenoxy) 3 pyrrolin-Z-one. Melting point, 149-151 C.

AlzalysiS.CalcCl. for C H Cl NO C, 54.56; H, 4.57. Found: C, 54.73; H, 4.63.

4,5,5 trimethyl 3 (2,4 dichlorophenoxy) 3 pyrrolin-2-one. Melting point, 127129 C.

Analysis.Calcd. for C H Cl NO C, 54.56; H, 4.57. Found: C, 54.79; H, 4.77.

4,5,5 trimethyl 3 (4 bromophenoxy) 3 pyrrolin-2-one. Melting point, 153155 C.

Analysis.--Calcd. for C H BrNO C, 52.72; H, 4.76. Found: C, 52.50; H, 4.78.

4,5,5 trimethyl 3 (4 fiuorophenoxy) 3 pyrrolin-2-one. Melting point, 139-141 C.

Analysis.-Calcd. for C H FNO C, 66.37; H, 5.99. Found: C, 66.51; H, 6.02.

1,4,5,5 tetramethyl 3 phenoxy 3 pyrrolin 2- one. Melting point, 64-66 C.

Analysis.Calcd. for C H NO C, 72.70; H, 7.40. Found: C, 72.92; H, 7.64.

1,4,5,5 tetramethyl 3 (3,4 dichlorophenoxy) 3- pyrrolin-2-one. Melting point, -87 C.

Analysis.Calcd. for C H CI NO C, 56.01; H, 5.03. Found C, 55.86; H, 5.25.

1,4,5,5 tetramethyl 3 (2,4 dichlorophenoxy) 3- pyrrolin-Z-one. Melting point, Ill-114 C.

Analysis.--Calcd. for C H Cl NO C, 56.01; H, 5.03. Found: C, 56.29; H, 5.27.

3 thienyl 4,5,5 trimethyl 3 pyrrolin 2 one. Melting point, l192 C.

Analysis.Calcd. for C H NOS: C, 63.73; H, 6.32. Found: C, 63.98; H, 6.31.

3 thienyl 1,4,5,5 tetramethyl 3 pyrrolin 2 one. Melting point, 62-64" C.

Analysis.Calcd. for C H NOS: C, 65.12; H, 6.83. Found: C, 65.33; H, 6.96.

The compounds of the present invention, when used to control crown gall, can be applied to the infected plant or they can be used prophylactically. For example, a suspension of the compound in water in a concentration of from about 2 parts per million to about 40 parts per million can be sprayed onto the ground at the base of the plant or onto the growing plant in an amount great enough to thoroughly drench the foliar parts of the plant and drip therefrom, thereby soaking the earth surrounding the crown of the plant. Alternatively, the compound in an aqueous suspension or dry powder formulation at 2 to 40 parts per million can be used as a dip for the seedlings during transplanting operations.

Concentrations of about /2 to about 8 pounds of the compounds of this invention per acre of soil can be used to prevent the invasion of certain monocotyledonous and dicotyledonous plants and weeds in lawns, gardens, and fields. The compounds, with or without an inert carrier, should be distributed evenly on the soil and can be in- Melting corporated, if desired, by methods well known in the art.

The compounds are also phytotoxic to certain mature dicotyledonous plants and can thus be used as a selective herbicide to control the spread of these plants. If used in this Way, they should be applied to the leaves of the plant at concentrations of about 1 to about 8 pounds per acre.

We claim: 1. A compound of the formula II It f (|TR m? R1 ()HaR wherein lower alkyl, C -C cycloalkyl, lower-alkoxy-lower alkyl, and tetrahydrofurfuryl; R is a member of the group consisting of hydrogen,

lower alkyl, phenyl, and naphthyl; and R is a member of the group consisting of phenyl,

monoand di-halo phenyl, phenoxy, monoand dihalo phenoxy, phenylthio, monoand di-halo phenylthio, naphthyl, monoand di-halo naphthyl, naphthyloxy, monoand di-halo naphthyloxy, naphthylthio, monoand di-halo naphthylthio, and thienyl. 2. 1,5,5 trimethyl 3 phenyl 4 ethyl 3 pyrrolin-2-one.

3. 4,5,5 trimethyl 3 (4 chlorophenylthio) 3- pyrrolin-Z-one.

4. 4,5,5 trimethyl 3 (3,4 dichlorophenyl) 3- pyrrolin-Z-one.

5. 4,5,5 trimethyl 3 (2,4 dichlorophenoxy) 3- pyrrolin-Z-one.

6. 3 (2 thienyl) 1,4,5,5 tetramethyl 3 pyrrolin- Z-one.

No references cited.

ALEX MAZEL, Primary Examiner.

HENRY R. JILES, Examiner.

JOSEPH A. NARCAVAGE, Assistant Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,272,842 September 13, 1966 Nelson R. Easton et all It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 1, line 60, for "C -C cycloalkyl" refers to cyclopropyl, cyclobutyl," read "C C cycloalkyl" refers to cyclopentyl, cyclohexyl, column 2, line 31, for "3- pentanone" read 2pentanone column 3, line 55, for "(3,4- dichlorophenoxy)" read (2,4-dich1orophenoxy) Signed and sealed this 1st day of August 1967.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. EDWARD J. BRENNER Attesting Officer Commissioner of Patents 

1. A COMPOUND OF THE FORMULA 